Epidermolysis Bullosa
All content on Eyewiki is protected by copyright law and the Terms of Service. This content may not be reproduced, copied, or put into any artificial intelligence program, including large language and generative AI models, without permission from the Academy.
Summary
Epidermolysis bullosa is group of inherited or acquired dermatoses characterized by dysfunction at the Dermal-epidermal junction that predisposes individuals to increased damage from mechanical trauma.[1] There are at least thirty epidermolysis bullosa subtypes organized within four major inherited groups. Patients with this condition have mucosal and skin fragility and can present with numerous ocular manifestations involving the conjunctiva and cornea. The ophthalmic complications vary with each subtype and treatment options can be complicated as the disease often presents in childhood and is chronic. These patients will often present to pediatric ophthalmology clinics for routine screening or with complications of the disease such as corneal abrasions, corneal scarring, corneal ulceration, symblepharon formation, and complications from eyelid scarring such as ectropion, entropion, or trichiasis. The management of these patients requires a multidisciplinary approach.
Subtypes of Disease
There are at least thirty epidermolysis bullosa subtypes organized within four major inherited groups:
- Epidermolysis Bullosa Simplex (70% of cases),
- Junctional Epidermolysis Bullosa (25% of cases)
- Dystrophic Epidermolysis Bullosa (5% of cases)
- Kindler Epidermolysis Bullosa (400 case reports worldwide.[2]
- The classifications are distinguished based on the anatomic location of disease in the cutaneous basement membrane zone, with Epidermolysis Bullosa Simplex occurring more superficially, Junctional Epidermolysis Bullosa occurring at the lamina lucida (between the basal cell plasma membrane and plasma densa), Dystrophic Epidermolysis Bullosa occurring below the lamina densa (with absent or reduced anchoring fibrils), and Kindler Epidermolysis Bullosa occurring at multiple levels.[3] [4]
Genetics
The modes of inheritance vary by subtype.
Generally, Epidermolysis Bullosa Simplex is inherited in an Autosomal Dominant fashion, Junctional Epidermolysis Bullosa is inherited in an autosomal recessive fashion, Dystrophic Epidermolysis Bullosa has been described to be inherited in both an Autosomal dominant and recessive fashion and Kindler Syndrome is typically autosomal dominantly inherited- although a few variants are recessively inherited.[4] [5]
Ocular Manifestations
The periocular and ocular surfaces are subject to similar shearing and blistering effects, and an array of symptoms have been described in the literature. Presentations of ocular disease are often related to mucosal surface fragility, with corneal lesions being the most common and serious finding as a result of its stratified squamous epithelium that is prone to mechanical-induced injuries in Epidermolysis Bullosa (Lin et al. 1994). The ocular disease was found to be most severe in dystrophic epidermolysis bullosa, with one review highlighting the Hallopeau-Siemens autosomal receive subtype which has little to no collagen type VII expression.[3][6] One review noted that 28/61 with recessive dystrophic epidermolysis bullosa had associated corneal lesions, while 9/12 of the patients with corneal pannus had the Hallopeau-Siemens subtype.[3] Refractive errors and amblyopia were also more common in the Hallopeau-Siemens subtype[3]
Associated ocular symptoms of Dystrophic Epidermolysis Bullosa[7][8][9][10] [11]
-Meibomian Gland Cysts
-Iris Cysts
-Retinal Detachment
-Focal loss of Retinal Pigment Epithelium
-Blepharitis
-Lid Ulceration
-Madarosis
-Lagophtlamolois
-Irregular Astigmastism
-Connjuctivocorneal blisters
-Limbal Broadening
-Cicatricial Conjuctival complications secondary to chronic conjunctivitis
-Lacrimal Stenosis
-Symblepahron
Ocular Treatment
The mainstay of ophthalmic treatment is ocular surface lubrication to prevent and protect corneal and mucous membrane erosion.
Early ocular intervention is recommended in patients with Epidermolysis Bullosa, as minor friction can cascade into corneal damage and ultimate visual acuity loss. Given that disease manifestation can occur as early as infancy, prompt recognition and treatment of sight-threatening processes such as corneal abrasion or symblepharon is crucial to preserve sight- with some patients responding well to surgical interventions like lamellar keratectomy and symblepharon lysis.[3] Other documented symptoms such as cataracts (seen across a variety of ages) and ectropion (due to blistering around eyelids) should be treated as encountered, with care that perioperative course and even simple measures such as glasses wearing can cause blistering.[3] Subtype-specific approaches are also important, as some techniques focused on treating the junctional epidermolysis bullosa of Herlitz utilize keratinocyte autografts for complete blister healing prior to ectropion repair.[12][13]
In some reports, Vitamin A has been used to help promote long term corneal healing.
Systemic treatment
Symptomatic disease treatment has been a mainstay modality of controlling the disease, principally via avoiding trauma and good wound care and disinfection.[14] Several clinical trials with curative intent are ongoing involving gene/cell therapy, but the best treatment options at this point involve close follow up with an interdisciplinary team and preventive measures from the patient[14]
In managing systemic symptoms, a few trials assessing topical and systemic treatment have been conducted. One small study showed modest benefit in blistering and erosion following granulocyte colony stimulating factor injection, and a clinical trial for this is ongoing.[15] Systemic treatment utilizing apremilast to target an underlying inflammatory nature of the condition was used in three patients with success in improving skin blistering.[14] [16] Several arms of clinical trials are in progress, all offering unique mechanisms to control both symptomatology and disease pathogenesis.
Follow Up
Follow-up with specialists should be pursued based on disease manifestations and baseline measurements for certain conditions , but the primary managers of the disease condition should a primary care physician in unison with a dermatologist with long term yearly follow up to provide the best outcomes[2][17] [18][19]
Prognosis
Prognosis varies based on disease subtype and complications from disease manifestations.[2]Thus, life expectancy can range from normal in milder disease manifestations/subtypes to mortality; the third to fifth decade of life following skin cancer development; and as early as childhood in severe junctional epidermolysis cases.[2] [20][21]
References
- ↑ Bardhan A, Bruckner-Tuderman L, Chapple ILC, Fine JD, Harper N, Has C, Magin TM, Marinkovich MP, Marshall JF, McGrath JA, Mellerio JE, Polson R, Heagerty AH. Epidermolysis bullosa. Nat Rev Dis Primers. 2020 Sep 24;6(1):78. doi: 10.1038/s41572-020-0210-0. PMID: 32973163.
- ↑ 2.0 2.1 2.2 2.3 Khanna, D., & Bardhan, A. (2024). Epidermolysis Bullosa. In StatPearls. StatPearls Publishing. /www.ncbi.nlm.nih.gov/books/NBK599531/
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Lin, A. N., Murphy, F., Brodie, S. E., & Carter, D. M. (1994). Review of Ophthalmic Findings in 204 Patients With Epidermolysis Bullosa. American Journal of Ophthalmology, 118(3), 384–390. /doi.org/10.1016/S0002-9394(14)72964-2
- ↑ 4.0 4.1 Stefanescu, B. I., Radaschin, D. S., Mitrea, G., Anghel, L., Beznea, A., Constantin, G. B., & Tatu, A. L. (2023). Epidermolysis Bullosa—A Kindler Syndrome Case Report and Short Literature Review. Clinics and Practice, 13(4), 873–880. /doi.org/10.3390/clinpract13040079
- ↑ Youssefian, L., Vahidnezhad, H., & Uitto, J. (1993). Kindler Syndrome. In M. P. Adam, J. Feldman, G. M. Mirzaa, R. A. Pagon, S. E. Wallace, L. J. Bean, K. W. Gripp, & A. Amemiya (Eds.), GeneReviews®. University of Washington, Seattle. /www.ncbi.nlm.nih.gov/books/NBK349072/
- ↑ Varki, R., Sadowski, S., Uitto, J., & Pfendner, E. (2007). Epidermolysis bullosa. II. Type VII collagen mutations and phenotype–genotype correlations in the dystrophic subtypes. Journal of Medical Genetics, 44(3), 181–192. /doi.org/10.1136/jmg.2006.045302
- ↑ Matsumoto, Y., Dogru, M., & Tsubota, K. (2005). Ocular Surface Findings in Hallopeau-Siemens Subtype of Dystrophic Epidermolysis Bullosa: Report of a Case and Literature Review. Cornea, 24(4), 474–479. /doi.org/10.1097/01.ico.0000151722.84634.bf
- ↑ COHEN, M., & SULZBERGER, M. B. (1935). ESSENTIAL SHRINKAGE OF CONJUNCTIVA IN A CASE OF PROBABLE EPIDERMOLYSIS BULLOSA DYSTROPHICA. Archives of Ophthalmology, 13(3), 374–390.
- ↑ McDonnell, P. J., & Spalton, D. J. (1988). The ocular signs and complications of epidermolysis bullosa. Journal of the Royal Society of Medicine, 81(10), 576–578.
- ↑ McDonnell, P. J., Schofield, O. M. V., Spalton, D. J., Mayou, B. J., & Eady, R. a. J. (1989). The eye in dystrophic epidermolysis bullosa: Clinical and immunopathological findings. Eye, 3(1), 79–83. /doi.org/10.1038/eye.1989.11
- ↑ Gans, L. A. (1988). Eye Lesions of Epidermolysis Bullosa: Clinical Features, Management, and Prognosis. Archives of Dermatology, 124(5), 762–764. /doi.org/10.1001/archderm.1988.01670050106033
- ↑ Lin, A. N., & Carter, D. M. (Eds.). (1992). Epidermolysis Bullosa: Basic and Clinical Aspects. Springer. /doi.org/10.1007/978-1-4612-2914-8
- ↑ Carter, D. M., Lin, A. N., Varghese, M. C., Caldwell, D., Pratt, L. A., & Eisinger, M. (1987). Treatment of junctional epidermolysis bullosa with epidermal autografts. Journal of the American Academy of Dermatology, 17(2 Pt 1), 246–250.
- ↑ 14.0 14.1 14.2 Bruckner-Tuderman L. Newer Treatment Modalities in Epidermolysis Bullosa. Indian Dermatol Online J. 2019 May-Jun;10(3):244-250. doi: 10.4103/idoj.IDOJ_287_18. PMID: 31149565; PMCID: PMC6536064.
- ↑ Efficacy of Granulocyte Colony Stimulating Factor (GCSF) In Patients With Dystrophic Epidermolysis Bullosa /clinicaltrials.gov/study/NCT01538862
- ↑ Castela E, Tulic MK, Rozières A, Bourrat E, Nicolas JF, Kanitakis J, Vabres P, Bessis D, Mazereeuw J, Morice-Picard F, Baty D, Berard F, Lacour JP, Passeron T, Chiaverini C. Epidermolysis bullosa simplex generalized severe induces a T helper 17 response and is improved by apremilast treatment. Br J Dermatol. 2019 Feb;180(2):357-364. doi: 10.1111/bjd.16897. Epub 2018 Dec 2. PMID: 29932457.
- ↑ Cicek N, Yildiz N, Asadov R, Yucelten AD, Tugtepe H, Alpay H. Kidney and Urinary Tract Involvement in Epidermolysis Bullosa: Is Routine Follow-Up Necessary? Dermatol Pract Concept. 2021 May 20;11(3):e2021051. doi: 10.5826/dpc.1103a51. PMID: 34123558; PMCID: PMC8172055.
- ↑ Ho G, Gibson M, Kazemikhoo N, Murrell DF. Long-term follow-up of epidermolysis bullosa in real practice shows stability of the Epidermolysis Bullosa Disease Activity and Scarring Index and improvement with some off-label therapies. JAAD Int. 2022 Sep 5;9:105-107. doi: 10.1016/j.jdin.2022.07.008. PMID: 36248204; PMCID: PMC9558050.
- ↑ Retrosi C, Diociaiuti A, De Ranieri C, Corbeddu M, Carnevale C, Giancristoforo S, Marchili MR, Salvatori G, Atti MLCD, El Hachem M, Raponi M. Multidisciplinary care for patients with epidermolysis bullosa from birth to adolescence: experience of one Italian reference center. Ital J Pediatr. 2022 Apr 12;48(1):58. doi: 10.1186/s13052-022-01252-3. PMID: 35414096; PMCID: PMC9006505.
- ↑ Yang CS, Kroshinksy D, Cummings BM. Neonatal junctional epidermolysis bullosa: treatment conundrums and ethical decision making. Am J Clin Dermatol. 2014 Oct;15(5):445-50. doi: 10.1007/s40257-014-0091-7. Erratum in: Am J Clin Dermatol. 2016 Jun;17(3):317. doi: 10.1007/s40257-016-0188-2. PMID: 25117154.
- ↑ Robertson SJ, Orrin E, Lakhan MK, O'Sullivan G, Felton J, Robson A, Greenblatt DT, Bernardis C, McGrath JA, Martinez AE, Mellerio JE. Cutaneous Squamous Cell Carcinoma in Epidermolysis Bullosa: a 28-year Retrospective Study. Acta Derm Venereol. 2021 Aug 24;101(8):adv00523. doi: 10.2340/00015555-3875. PMID: 34230977; PMCID: PMC9413672.
